Plasma apolipoprotein(a) concentrations are influenced by genetic factors, particularly Kringle IV polymorphism, and non-genetic factors including thyroid hormones. While plasma apo(a) concentrations are increased even in subclinical hypothyroidism, and low plasma concentrations present in hyperthyroidism increase after treatment, it is unclear whether there are differential or parallel effects on apo(a) isoforms of different size. We investigated this using high resolution apo(a) phenotyping. In 30 hyperthyroid patients, plasma apo(a) concentrations increased after radioiodine treatment, mean 78.6 (range 17-458) U/I at baseline vs 132.3 (17- 1078) U/I at 3 months (P<0.001). In five subjects with transient hypothyroidism, plasma apo(a) increased further, while in 11 patients with recurrent hyperthyroidism, 6 months post treatment plasma apo(a) concentrations declined again. High resolution SDS-agarose gel electrophoresis used to define apo(a) KIV size phenotypes showed 14 different isoforms ranging from KIV 16 to KIV 37. Two isoforms were present in 57% of patients. During treatment, changes in apo(a) isoforms paralleled those of plasma apo(a) concentrations and affected both large (KIV 29-37) and small (KIV 16-25) isoforms. In patients with two isoforms, both changed in parallel. Rises in plasma apo(a) concentrations lagged behind LDL cholesterol rises. This suggests that the thyroxine effects on plasma apo(a) concentrations are unlikely to be mediated via effects on the LDL receptor, which affect predominantly LDL catabolism. In conclusion, plasma apo(a) concentrations increased during treatment of hyperthyroidism, but more slowly than LDL. This effect on apo(a) applied to all apo(a) isoforms, large and small, with changes occurring in parallel rather than differentially when two isoforms were present in any one individual.

Plasma apolipoprotein(a) concentrations are influenced by genetic factors, particularly Kringle IV polymorphism, and non-genetic factors including thyroid hormones. While plasma apo(a) concentrations are increased even in subclinical hypothyroidism, and low plasma concentrations present in hyperthyroidism increase after treatment, it is unclear whether there are differential or parallel effects on apo(a) isoforms of different size. We investigated this using high resolution apo(a) phenotyping. In 30 hyperthyroid patients, plasma apo(a) concentrations increased after radioiodine treatment, mean 78.6 (range 17-458) U/I at baseline vs 132.3 (17- 1078) U/I at 3 months (P<0.001). In five subjects with transient hypothyroidism, plasma apo(a) increased further, while in 11 patients with recurrent hyperthyroidism, 6 months post treatment plasma apo(a) concentrations declined again. High resolution SDS-agarose gel electrophoresis used to define apo(a) KIV size phenotypes showed 14 different isoforms ranging from KIV 16 to KIV 37. Two isoforms were present in 57% of patients. During treatment, changes in apo(a) isoforms paralleled those of plasma apo(a) concentrations and affected both large (KIV 29-37) and small (KIV 16-25) isoforms. In patients with two isoforms, both changed in parallel. Rises in plasma apo(a) concentrations lagged behind LDL cholesterol rises. This suggests that the thyroxine effects on plasma apo(a) concentrations are unlikely to be mediated via effects on the LDL receptor, which affect predominantly LDL catabolism. In conclusion, plasma apo(a) concentrations increased during treatment of hyperthyroidism, but more slowly than LDL. This effect on apo(a) applied to all apo(a) isoforms, large and small, with changes occurring in parallel rather than differentially when two isoforms were present in any one individual.

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eng

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Endocrinology and Metabolism

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dc.title

The effect of radioiodine treatment of hyperthyroidism on plasma apolipoprotein(a) concentrations and phenotypic expression